Several reports have recently appeared disclosing that HMB exhibits significant efficacy for nitrogen retention and muscle building in humans. See Nissen et al., U.S. Pat. No. 5,348,979; Phillips, Muscle Media 2000 (October 1995), "HMB New Drug-Free Mass Builder;" these and all other references cited herein are expressly incorporated by reference as if fully set forth in their entirety herein. Promoting nitrogen retention has therapeutic importance for trauma patients and for patients showing loss of protein due to stress conditions. Moreover, administration of HMB has been reported to enhance the immune response of mammals (Nissen et al., U.S. Pat. No. 4,992,470), and to increase lean tissue development in meat-producing animals (Nissen et al., U.S. Pat. Nos. 5,087,472 and 5,028,440).
The structure of HMB is reproduced below. ##STR1##
Despite these several reports on the beneficial properties of HMB, this substance is currently available only in small quantities due to the lack of a suitable synthetic procedure for commercial production of HMB. In fact, during recent years, several chemical manufacturing companies have sought to develop a high output synthetic process for HMB. These attempts have been based on the reactions described in Coffinan et al., Journal of the American Chemical Society 80:2882-2887 (1958); Wagner & Zook, Synthetic Organic Chemistry 422-423, 458 (1953); March, Advanced Organic Chemistry, Rxn. 2-43, 567 (3d ed. 1985); Blatt, Organic Synthesis 2:428429, 526-527 (1943); Blatt, Organic Synthesis 3:302-303 (1955) Blatt, Organic Synthesis 5:8-9 (1973). According to this procedure, diacetone alcohol (DIA) is subjected to alkaline sodium hypochlorite oxidation to produce HMB.
In a previous attempt at producing a commercially viable procedure, an average yield of 0.26 pounds of HMB per pound of DIA was achieved, with the most efficient batch achieving a yield of 0.325 pounds of HMB per pound of DIA. The reaction was typically run in a reactor no greater than 200 gallons, with an average charge of 156 gallon of bleach and about 95 pounds of DIA, to produce about 25 pounds HMB per batch. This process was plagued by an inability to control reaction temperature, and this inability mandated the use of small batch sizes. This process moreover failed to provide access to HMB in quantities sufficient to enable therapy on humans or animals. Thus, a need exists for an HMB manufacturing process that will allow production of high quantities of high quality HMB, and will permit HMB manufacture on a large scale, has been achieved through the improvements described herein.